ArticleNeurochemical research2015
Characterization of the neuroprotective potential of derivatives of the iron chelating drug deferiprone.
Article in Neurochemical research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Iron and Targeted Iron Therapy in Alzheimer's Disease.International journal of molecular sciences · 2023Review
- The Vital Role Played by Deferiprone in the Transition of Thalassaemia from a Fatal to a Chronic Disease and Challenges in Its Repurposing for Use in Non-Iron-Loaded Diseases.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Deferiprone and Iron-Maltol: Forty Years since Their Discovery and Insights into Their Drug Design, Development, Clinical Use and Future Prospects.International journal of molecular sciences · 2023Review
- Deferiprone: A Forty-Year-Old Multi-Targeting Drug with Possible Activity against COVID-19 and Diseases of Similar Symptomatology.International journal of molecular sciences · 2022Review
- Synthesis, physicochemical characterization and neuroprotective evaluation of novel 1-hydroxypyrazin-2(1Dalton transactions (Cambridge, England : 2003) · 2022Article
- The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress.Frontiers in pharmacology · 2022Review
- Antioxidant Activity of Deferasirox and Its Metal Complexes in Model Systems of Oxidative Damage: Comparison with Deferiprone.Molecules (Basel, Switzerland) · 2021Article
- Copper Dyshomeostasis in Neurodegenerative Diseases-Therapeutic Implications.International journal of molecular sciences · 2020Review
- Review
- Advances on Chelation and Chelator Metal Complexes in Medicine.International journal of molecular sciences · 2020Article
- Current Biomedical Use of Copper Chelation Therapy.International journal of molecular sciences · 2020Review
- The History of Deferiprone (L1) and the Paradigm of the Complete Treatment of Iron Overload in Thalassaemia.Mediterranean journal of hematology and infectious diseases · 2020Review
- Effective inhibition of copper-catalyzed production of hydroxyl radicals by deferiprone.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2019Article
- The role of CaCell calcium · 2018Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is growing evidence for alterations in iron homeostasis during aging that are exacerbated in neurodegenerative diseases such as Alzheimer's disease. However, since essentially all neurodegenerative diseases are multi-factorial in the sense that there are a large number of mechanisms that can be identified as contributing to nerve cell death, iron chelators that have additional activities might be the most useful for the treatment of age-related CNS diseases. We have described a series of cell culture-based assays that define molecular toxicity pathways relevant to neurodegenerative diseases and have used these assays to identify potential therapeutic compounds for the treatment of these diseases. Deferiprone is a blood brain barrier permeable, low molecular weight iron chelator that has been used for many years to treat systemic iron disease. In this study, we describe the use of our cell culture-based screening assays to identify deferiprone derivatives with the greatest therapeutic potential for the treatment of CNS diseases. We show that several derivatives are much more potent than deferiprone at reducing oxidative stress and preventing nerve cell death induced by multiple, age-related insults. In addition, we show that both deferiprone and the derivatives modulate several distinct signaling pathways associated with neuroprotection. All of the compounds were able to both inhibit the activation of p38 MAP kinase and JNK kinase and prevent the loss of PI3 kinase activity in response to a toxic stress. These results strongly suggest that these compounds have significant potential for the treatment of CNS diseases.
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